title: Characterization of the gut-associated microbiome in inflammatory pouch complications following ileal pouch-anal anastomosis.
abstract: BACKGROUND
  Inflammatory complications following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) are common and thought to arise through mechanisms similar to de novo onset inflammatory bowel disease. The aim of this study was to determine whether specific organisms in the tissue-associated microbiota are associated with inflammatory pouch complications.
  
  
  METHODS
  Patients having previously undergone IPAA were recruited from Mount Sinai Hospital. Clinical and demographic information were collected and a pouchoscopy with biopsy of both the pouch and afferent limb was performed. Patients were classified based on post-surgical phenotype into four outcome groups: familial adenomatous polyposis controls (FAP), no pouchitis, pouchitis, and Crohn's disease-like (CDL). Pyrosequencing of the 16S rRNA V1-V3 hypervariable region, and quantitative PCR for bacteria of interest, were used to identify organisms present in the afferent limb and pouch. Associations with outcomes were evaluated using exact and non-parametric tests of significance.
  
  
  RESULTS
  Analysis at the phylum level indicated that Bacteroidetes were detected significantly less frequently (P<0.0001) in the inflammatory outcome groups (pouchitis and CDL) compared to both FAP and no pouchitis. Conversely, Proteobacteria were detected more frequently in the inflammatory groups (P=0.01). At the genus level, organisms associated with outcome were detected less frequently among the inflammatory groups compared to those without inflammation. Several of these organisms, including Bacteroides (P<0.0001), Parabacteroides (P≤2.2x10(-3)), Blautia (P≤3.0x10(-3)) and Sutterella (P≤2.5x10(-3)), were associated with outcome in both the pouch and afferent limb. These associations remained significant even following adjustment for antibiotic use, smoking, country of birth and gender. Individuals with quiescent disease receiving antibiotic therapy displayed similar reductions in these organisms as those with active pouch inflammation.
  
  
  CONCLUSIONS
  Specific genera are associated with inflammation of the ileal pouch, with a reduction of typically ubiquitous organisms characterizing the inflammatory phenotypes.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada ; Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital Inflammatory Bowel Disease Group, Toronto, Ontario, Canada.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Tyler
authors.forename: Natalie
authors.initials: N
authors.lastname: Knox
authors.forename: Boyko
authors.initials: B
authors.lastname: Kabakchiev
authors.forename: Raquel
authors.initials: R
authors.lastname: Milgrom
authors.forename: Richard
authors.initials: R
authors.lastname: Kirsch
authors.forename: Zane
authors.initials: Z
authors.lastname: Cohen
authors.forename: Robin S
authors.initials: RS
authors.lastname: McLeod
authors.forename: David S
authors.initials: DS
authors.lastname: Guttman
authors.forename: Denis O
authors.initials: DO
authors.lastname: Krause
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000382:microbiology* / Q000601:surgery; D000714:Anastomosis, Surgical / Q000009:adverse effects*; D005260:Female; D005767:Gastrointestinal Diseases / Q000601:surgery*; D006801:Humans; D007082:Ileum / Q000382:microbiology* / Q000601:surgery; D007249:Inflammation / Q000209:etiology* / Q000382:microbiology; D008297:Male; D064307:Microbiota; D008875:Middle Aged